It is said that the cost for developing pharmaceutical products has exponentially increased in recent years in accordance with Eroom's law (NPL 1). Considering the fact that the probability of dropout of the development of pharmaceutical products at the clinical testing stage is increasing every year (NPL 2) or the problem of differences between species in animal testing, it is expected that in-vitro assay using cultured cells will be increasingly important in the future.
Currently, as a high-throughput system is becoming widespread, a cellular assay is widely used in a case of drug discovery screening. In recent years, a liquid handling technique such as an inkjet method has become usable, and hence the throughput is further increasing. Furthermore, there is a trend toward a high-content screening technique which makes it possible to obtain more information through a single assay.
However, in the monolayer culture used in the general cellular assay, the surrounding environment of the cell is greatly different from the internal environment of an animal, and this leads to a problem in that the cultured cell loses many of its functions which are supposed to be expressed in the body of the animal.
In next generation cellular assay techniques, an assay with higher reliability is adopted which uses a tissue having a higher function by artificially reconstructing a tissue imitating a three-dimensional structure in a biological body. Accordingly, an in vivo-in vitro correlation is expected to become stronger.
As one of the cell culture methods, there is a method of using a hydrogel. Due to the characteristics such as a high moisture content, ease of adjusting dynamic properties, and excellent nutrient diffusivity, the hydrogel is excellent as a cell carrier (NPL 3).
By the incorporation of a photodegradable group into the hydrogel molecule, the hydrogel obtains photodegradability, and in this way, a photodegradable gel which can be optically processed is developed. For example, there is a photodegradable gel which has polyethylene glycol as a main chain and contains a nitrobenzyl group in a molecule (PTL 1 and NPL 4). The physical properties of the hydrogel formed of a polymer monomer constituted as above can be controlled in terms of time and space by light irradiation (NPL 5 and 6), and the photodegradability is highly compatible with a living cell (NPL 4 and 7).
However, because the photodegradable gels reported so far are gelated by means of radical polymerization, they deteriorate in some cases by being influenced by oxygen when they are polymerized in the presence of oxygen. Furthermore, a radical damages cells or bioactive substances. In addition, because the polymer compound usable as a main chain is restricted to a polymer of a radically polymerizable monomer, there is a problem that the use thereof is limited.
The inventors of the present invention have developed a photodegradable cross-linking agent which can form a photodegradable gel by causing a cross-linking reaction simply by being mixed with a polymer compound without using radical polymerization (PTL 2).